Non-volatile memory (NVM) will play a decisive role in the development of the next-generation of electronic products. Therefore, the development of next-generation NVM is urgent as widely applied ...flash memory is facing its physical limit. Among various next-generation NVMs, Resistive Random Access Memory (RRAM) is a promising candidate for future memory due to its high-efficiency, high-speed and energy-saving characteristics. In recent years, continuous improvement and in-depth investigation in both materials and electrical switching mechanisms have not only lead to a breakthrough in the performance of digital NVM, but also lead to other possible memory functionality. This paper describes new findings and perspectives on various RRAM devices with different laminated structures and materials, and classifies RRAM into four categories according to different resistive switching mechanisms, from which the four elements are (1) anion-type RRAM: redox reaction and migration of oxygen ions, (2) cation-type RRAM: redox reaction and migration of cation ions, (3) carbon-based RRAM: the stretch of CC bond lengths due to oxygen and hydrogen dual ions, (4) oxide-based electrode: oxygen accumulation in oxide-based electrode.
Pancreatic neuroendocrine tumor (pNET) is a pancreatic neoplasm with neuroendocrine differentiation. pNET in early stage can be treated with surgical resection with long‐term survival, whereas the ...prognosis of pNET with locoregional or distant metastasis is relatively poor. Lymphangiogenesis is essential for tumor metastasis via the lymphatic system and may overhead distant metastasis. c‐Myc overexpression is involved in tumorigenesis. The role of c‐Myc in lymphangiogenesis is unclear. In this study, we evaluated the mechanism and effect of c‐Myc on lymphangiogenesis of pNET via interaction of lymphatic endothelial cells (LECs) and pNET cells. Lymph node metastasis was evaluated in pNET xenograft mice. Potential target agents to inhibit lymph node metastasis were evaluated in an animal model. We found that vascular endothelial growth factor C (VEGFC) expression and secretion was increased in pNET cell lines with c‐Myc overexpression. c‐Myc transcriptionally upregulates VEGFC expression and the secretion of pNET cells by directly binding to the E‐box of the VEGFC promoter and enhances VEGF receptor 3 phosphorylation and the tube formation of LECs. c‐Myc overexpression is associated with lymph node metastasis in pNET xenograft mice. Combinational treatment with an mTOR inhibitor and c‐Myc inhibitor or VEGFC‐neutralizing chimera protein reduced lymph node metastasis in the mice with c‐Myc overexpression. The mTOR inhibitor acts on lymphangiogenesis by reducing VEGFC expression in pNET cells and inhibiting the tube formation of LECs. In conclusion, mTOR and c‐Myc are important for lymphangiogenesis of pNET and are potential therapeutic targets for prevention and treatment of lymph node metastasis in pNET.
c‐Myc promotes lymph node metastases of pancreatic neuroendocrine tumors via upregulation of vascular endothelial growth factor C (VEGFC). Combined targeting of mTOR with c‐Myc or VEGFC is a potential therapy for the treatment of pNET.
This meta-analysis examined roles of several metabolites in differentiating recurrent tumor from necrosis in patients with brain tumors using MR perfusion and spectroscopy.
Medline, Cochrane, EMBASE, ...and Google Scholar were searched for studies using perfusion MRI and/or MR spectroscopy published up to March 4, 2015 which differentiated between recurrent tumor vs. necrosis in patients with primary brain tumors or brain metastasis. Only two-armed, prospective or retrospective studies were included. A meta-analysis was performed on the difference in relative cerebral blood volume (rCBV), ratios of choline/creatine (Cho/Cr) and/or choline/N-acetyl aspartate (Cho/NAA) between participants undergoing MRI evaluation. A χ2-based test of homogeneity was performed using Cochran's Q statistic and I2.
Of 397 patients in 13 studies who were analyzed, the majority had tumor recurrence. As there was evidence of heterogeneity among 10 of the studies which used rCBV for evaluation (Q statistic = 31.634, I2 = 97.11%, P < 0.0001) a random-effects analysis was applied. The pooled difference in means (2.18, 95%CI = 0.85 to 3.50) indicated that the average rCBV in a contrast-enhancing lesion was significantly higher in tumor recurrence compared with radiation injury (P = 0.001). Based on a fixed-effect model of analysis encompassing the six studies which used Cho/Cr ratios for evaluation (Q statistic = 8.388, I2 = 40.39%, P = 0.137), the pooled difference in means (0.77, 95%CI = 0.57 to 0.98) of the average Cho/Cr ratio was significantly higher in tumor recurrence than in tumor necrosis (P = 0.001). There was significant difference in ratios of Cho to NAA between recurrent tumor and necrosis (1.02, 95%CI = 0.03 to 2.00, P = 0.044).
MR spectroscopy and MR perfusion using Cho/NAA and Cho/Cr ratios and rCBV may increase the accuracy of differentiating necrosis from recurrent tumor in patients with primary brain tumors or metastases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To assess the use of the dual-energy computed tomographic (CT) virtual noncalcium technique in the evaluation of bone marrow edema in vertebral compression fractures.
This prospective study was ...approved by the institutional review board; informed consent was obtained from all patients. Sixty-three consecutive patients with 112 thoracic and/or lumbar vertebral compression fractures were studied between January 2011 and April 2012. All patients underwent both dual-energy CT (100 kV and Sn140 kV, where Sn indicates the use of a 0.4-mm tin filter) and magnetic resonance (MR) imaging. Dual-energy CT data were postprocessed by using a three-material decomposition algorithm for generating noncalcium images of the collapsed bodies. Two radiologists evaluated for the presence of abnormal attenuation alterations in the bone marrow by using color-coded maps and measured CT numbers on noncalcium grayscale images. Bone sclerosis and intravertebral air were evaluated with CT scans. MR images served as the reference standard. CT numbers were subjected to receiver operating characteristic curve analysis.
MR imaging depicted 46 edematous and 66 nonedematous vertebral compression fractures. Eighty-two bodies were classified as having less than 50% sclerosis and/or air. Significant differences in noncalcium CT numbers between edematous and nonedematous vertebral compression fractures were found for both readers (P < .0001). CT numbers for the diagnosis of bone marrow edema on the basis of MR imaging revealed areas under the receiver operating characteristic curve of 0.799 and 0.841 for readers 1 and 2, respectively (P = .56). Use of a cutoff value of -80 to differentiate edematous vertebral bodies resulted in a sensitivity of 96.3%, specificity of 98.2%, and accuracy of 97.6% in the group of vertebral bodies with less than 50% sclerosis and/or air.
Dual-energy CT virtual noncalcium images were able to depict bone marrow in the collapsed vertebral bodies, especially in those with less than 50% sclerosis and/or air.
Metformin is proposed to have chemopreventive effect of various cancer currently. However, the anti-cancer effect of metformin for diabetic patients with hepatocellular carcinoma (HCC) undergoing ...liver resection remains unclear. The aim of our cohort study was to assess whether metformin influence the recurrence of HCC.
We retrospectively enrolled 857 HCC patients who received primary resection from April 2001 to June 2016. 222 patients were diagnosed with diabetes mellitus (DM) from medical record. Factors influence the overall survival (OS) and recurrence-free survival (RFS) were analyzed by multivariate analysis.
During the follow-up period (mean, 75 months), 471 (54.9%) patients experienced recurrence, and 158 (18.4%) patients died. Multivariate analysis revealed that DM (p = 0.015), elevated AST (p = 0.006), hypoalbuminemia (p = 0.003), tumor number (p = 0.001), tumor size (p < 0.001), vascular invasion (p <0.001), high Ishak fibrosis score (p <0.001), hepatitis B (p = 0.014), hepatitis C (p = 0.001) were independent predictors for RFS. In diabetic patients, only HbA1c>9% (p = 0.033), hypoalbuminemia (p = 0.030) and vascular invasion (p = 0.001) were independent risk factors for HCC recurrence; but the metformin use revealed no significance on recurrence. DM is a risk factor of HCC recurrence after resection. Adequate DM control can reduce the recurrence of HCC. However, the use of metformin does not reduce the risk of HCC recurrence in diabetic patient after initial resection. Hence, metformin may not have protective influences on HCC recurrence in diabetic patients who undergo initial liver resection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Nonvolatile stateful logic through RRAM is a promising route to build in-memory computing architecture. In this letter, a logic methodology based on 1T1R structure has been proposed to implement ...functionally complete Boolean logics. Arbitrary logic functions could be realized in two steps: initialization and writing. An additional read step is required to read out the logic result, which is in situ stored in the nonvolatile resistive state of the memory. Cascade problem in building larger logic circuits is also discussed. Our 1T1R logic device and operation method could be beneficial for massive integration and practical application of RRAM-based logic.
To evaluate the effects of metformin use on the survival of inoperable non-small cell lung cancer (NSCLC) patients with diabetes using the Taiwanese National Health Insurance Research Database.
In ...total, 7,620 patients were eligible in this study, among them, 3,578 patients were metformin users and 4,042 were non-users. Propensity score matching was used to reduce possible confounding factors. In total, 4,182 patients (2,091 matched pairs) were included in the matched cohort. Cox proportional hazard model with time-dependent covariate were also applied to evaluate the association between metformin use and overall survival (OS).
A total of 3,578 patients were metformin users at the time of diagnosis of NSCLC. Cox proportional hazard model with time-dependent covariate revealed that metformin use was associated with a significantly longer OS (HR: 0.85, 95.0% CI: 0.80-0.90). The survival benefit of metformin use was maintained after propensity score matching at a ratio of 1:1 (HR: 0.90, 95.0% CI: 0.84-0.97).
Metformin use is associated with longer OS in inoperable NSCLC patients with diabetes, suggesting a potential anti-tumorigenic effect for metformin. Further research is needed to investigate the actual role of metformin in the treatment of NSCLC patients with diabetes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Tumor cells may aberrantly express metabolic enzymes to adapt to their environment for survival and growth. Targeting cancer‐specific metabolic enzymes is a potential therapeutic strategy. ...Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes the conversion of oxaloacetate to phosphoenolpyruvate and links the tricarboxylic acid cycle and glycolysis/gluconeogenesis. Mitochondrial PEPCK (PEPCK‐M), encoded by PCK2, is an isozyme of PEPCK and is distributed in mitochondria. Overexpression of PCK2 has been identified in many human cancers and demonstrated to be important for the survival program initiated upon metabolic stress in cancer cells. We evaluated the expression status of PEPCK‐M and investigated the function of PEPCK‐M in breast cancer.
Methods
We checked the expression status of PEPCK‐M in breast cancer samples by immunohistochemical staining. We knocked down or overexpressed PCK2 in breast cancer cell lines to investigate the function of PEPCK‐M in breast cancer.
Results
PEPCK‐M was highly expressed in estrogen receptor‐positive (ER+) breast cancers. Decreased cell proliferation and G0/G1 arrest were induced in ER+ breast cancer cell lines by knockdown of PCK2. PEPCK‐M promoted the activation of mTORC1 downstream signaling molecules and the E2F1 pathways in ER+ breast cancer. In addition, glucose uptake, intracellular glutamine levels, and mTORC1 pathways activation by glucose and glutamine in ER+ breast cancer were attenuated by PCK2 knockdown.
Conclusion
PEPCK‐M promotes proliferation and cell cycle progression in ER+ breast cancer via upregulation of the mTORC1 and E2F1 pathways. PCK2 also regulates nutrient status‐dependent mTORC1 pathway activation in ER+ breast cancer. Further studies are warranted to understand whether PEPCK‐M is a potential therapeutic target for ER+ breast cancer.
PEPCK‐M was highly expressed in ER+ breast cancer patients. PEPCK‐M promotes the proliferation and cell cycle progression of ER+ breast cancer via upregulation of the mTORC1 and E2F1 pathways. PCK2 is also involved in the regulation of mTORC1 pathway activation by nutrition status in ER+ breast cancer cells. Further study is warranted to understand whether PEPCK‐M can be a potential target for the treatment of ER+ breast cancer.
Urokinase plasminogen activator (uPA) is an extracellular matrix-degrading protease that is involved in the invasiveness and progression of cancer. There is good evidence that uPA expression is a ...clinically relevant biomarker in some solid tumors, but its role in hepatocellulcar carcinoma (HCC) is uncertain. We evaluated the prognostic value of serum uPA before surgery in HCC patients receiving curative resection.
Serum uPA levels were determined by enzyme-linked immunosorbent assay in 282 HCC patients who received complete liver resections at Kaohsiung Chang Gung Memorial Hospital. Overall survival (OS) curves were constructed using the Kaplan-Meier method and compared using the log-rank test. A Cox proportional -hazards regression model was used to identify independent prognostic factors. The median follow-up time was 52 months.
Patients with higher pretreatment serum uPA (≥1 ng/ml) had significantly shorter OS (p = 0.002). Patients with liver cirrhosis, hypoalbuminemia, and thrombocytopenia were significantly more likely to present with elevated uPA levels. Multivariate Cox regression analyses indicated that high pretreatment serum uPA hazard ratio (HR), 1.848, p = 0.006, vascular invasion (HR, 2.940, p < 0.001), and pathology stage III/IV (HR, 3.517, p < 0.001) were independent prognostic factors for OS. In further stratified analyses, the combination of serum uPA and AFP had more capacity to predict OS.
We conclude that uPA is a clinically relevant biomarker in HCC patients receiving curative resection, with higher expression of uPA being associated with higher mortality. This also highlights the potential utility of uPA as a therapeutic target for improved treatment strategies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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